SUBSTITUTED INDOLE OXO-ACETYL AMINO ACETIC ACID DERIVATIVES AS INHIBITORS OF PLASMINOGEN ACTIVATOR INHIBITOR-1 (PAI-1)

摘要

This invention provides indole oxo-acetyl amino acetic acid derivatives which are useful as inhibitors of plasminogen activator inhibitor-1 (PAI-1) useful for treating fibrinolytic disorders, the compounds having the structure: wherein: RSUB1 /SUBis alkyl or optionally substituted cycloalkyl, -CHSUB2/SUB-cycloalkyl, pyridinyl, -CHSUB2/SUB-pyridinyl, phenyl or benzyl; RSUB2 /SUBis hydrogen, alkyl, cycloalkyl, -CHSUB2/SUB-cycloalkyl, or perfluoroalkyl; RSUB3 /SUBis hydrogen, halo, alkyl, perfluoroalkyl, alkoxy, cycloalkyl, -CHSUB2/SUB-cycloalkyl, -NHSUB2/SUB, or -NOSUB2/SUB; RSUB4 /SUBis optionally substituted phenyl, benzyl, benzyloxy, pyridinyl, or -CHSUB2/SUB-pyridinyl; RSUB8 /SUBis hydrogen, alkyl, cycloalkyl, -CHSUB2/SUB-cycloalkyl, perfluoroalkyl, aryl, substituted aryl, alkyl-aryl, or substituted alkyl-aryl; RSUB9 /SUBis hydrogen, alkyl, hydroxyalkyl, 4-hydroxybenzyl, 3-indolylymethylene, 4-imidazolylmethylene, HSCHSUB2/SUB-, CHSUB3/SUBSCHSUB2/SUBCHSUB2/SUB-, HSUB2/SUBNC(-O)CHSUB2/SUB-, HSUB2/SUBNC(-O)CHSUB2/SUBCHSUB2/SUB-, HOSUB2/SUBCCHSUB2/SUB-, HOSUB2/SUBCCHSUB2/SUBCHSUB2/SUB-, HSUB2/SUBNCHSUB2/SUBCHSUB2/SUBCHSUB2/SUBCHSUB2/SUB-, HSUB2/SUBNC(-NH)NHCHSUB2/SUBCHSUB2/SUBCHSUB2/SUB-, or taken together with RSUB8 /SUBas -CHSUB2/SUBCHSUB2/SUBCHSUB2/SUB-; or a pharmaceutically acceptable salt or ester form thereof.